Central Autonomic Network Regions and Hypertension: Unveiling Sympathetic Activation and Genetic Therapeutic Perspectives

SIMPLE SUMMARY: High blood pressure, or hypertension, is a serious condition with potentially life-threatening consequences. Researchers conducted a study to explore how certain areas of the brain contribute to high blood pressure. The focus was on three specific brain regions: the lateral parabrachial nucleus (LPBN), Kolliker-fuse nucleus (KF), and periductal grey matter (PAG), which play roles in regulating blood pressure. Using genetic modification techniques, the researchers decreased the neuronal activity in these brain regions. They observed interesting outcomes: reducing activity in the LPBN led to significant decreases in blood pressure and heart rate; in the KF, the activity of the nerves involved in blood pressure regulation and breathing decreased; however, reducing activity in the PAG did not have a significant impact on blood pressure, but affected the heart’s response to changes in blood pressure. These findings highlight the importance of specific brain areas, particularly the LPBN, in regulating blood pressure. While this study was conducted on rats and further research is needed to apply these findings to humans, it provides valuable insights into the complex factors contributing to high blood pressure. This knowledge could potentially pave the way for future treatments and interventions targeting these brain regions in order to better manage hypertension. ABSTRACT: Introduction: Hypertension, a leading cause of death, was investigated in this study to understand the role of specific brain regions in regulating blood pressure. The lateral parabrachial nucleus (LPBN), Kolliker-fuse nucleus (KF), and periductal grey matter (PAG) were examined for their involvement in hypertension. Methods: Lentiviral vectors were used to alter the activity of these brain regions in hypertensive rats. Over a 75-day period, blood pressure, heart rate, reflex responses, and heart rate variability were measured. Results: Decreasing the activity in the LPBN resulted in a reduced sympathetic outflow, lowering the blood pressure and heart rate. In the KF, the sympathetic activity decreased and chemoreflex variation was attenuated, without affecting the blood pressure. Silencing the PAG had no significant impact on blood pressure or sympathetic tone, but decreased cardiac baroreflex gain. Discussion: These findings highlight the significant role of the LPBN in hypertension-related sympathetic activation. Additionally, LPBN and KF neurons appear to activate mechanisms that control respiration and sympathetic outflow during chemoreceptor activation. Conclusions: The study provided insights into the contribution of the midbrain and pontine regions to neurogenic hypertension and offers potential avenues for future genetic interventions and developing novel treatment approaches.